The purpose of this project is to develop improved drug therapies for nervous system disease. Towards this end investigations seek to determine the relationship between dysfunction of a particular neurohumoral pathway and the presence of a specific neurologic sign. In addition, the ability of newly available pharmacologic agents to safely influence activity in specific transmitter systems in the central nervous system of man is investigated. Major topics under study include: 1) Use of a stable isotope of oxygen (18O2) to evaluate central monoamine metabolism in man. 2) Relation of monoamine and peptide neurotransmitters to specific motor, sensory, behavioral, or endocrinologic functions. 3) Ability of putative agonists and antagonists of neural systems mediated by dopamine, serotonin, acetylcholine, and gamma aminobutyric acid, to selectively influence synaptic transmission in these systems and improve various disorders of central nervous system function. 4) Presymptomatic diagnostic tests for Huntington's disease.